The character's original CBS biography (which has since been removed) stated that she was born in Bozeman, Montana on March 26, 1963 and raised by her mother, Lily Flynn (Anita Gillette), a former show girl ("Weeping Willows", "Kiss-Kiss, Bye-Bye"). This biography was later revised. The new version states that the character was born in Las Vegas and raised by her single mother, who worked as a cocktail waitress and showgirl at various jobs along the west coast.

The seventh-season episode "Living Legend" established that Willows was 16 years old (portrayed by Amy Scott) in 1975, the year the movie Jaws was released, which places her year of birth in either 1958 or 1959. She had occasional contact with her biological father, casino owner Sam Braun, but knew him only as a family friend. Sam Braun nicknamed her "Muggs". She did not learn he had fathered her until she was an adult and compared his DNA sample with her own as part of a murder investigation in the episode "Inside the Box". Willows herself worked for a time as a dancer/stripper and briefly had a cocaine habit, dropping it before pursuing a Bachelor of Science in Medical Technology from UNLV. Like the other characters on CSI, she has a wide knowledge of odd facts that help in their investigations of crime scenes.

The show's Writers advanced Lindsey's age several years after the death of Eddie, turning the character from preteen to teenager. Willows's relationship with Lindsey soured somewhat after Eddie's murder, and the girl's behavior took a turn for the worse; she would get in fights at school and was once picked up for hitchhiking. Willows took Lindsey to the Morgue and showed her the body of a murder victim to impress upon Lindsey the danger of her behavior. Willows later enrolled Lindsey in Butterfield ("4 x 4"), a private school that would keep a tighter rein on her. Lindsay's birthday was mentioned in "Crate 'N' Burial" on October 20, 2000.

For her portrayal of Catherine, Helgenberger received two Golden Globe Award nominations for Best Actress in a Television Series Drama in 2001 and 2002. At the 6th Golden Satellite Awards, Helgenberger was nominated for Best Actress in a Drama Series. She also earned two Primetime Emmy Award nominations for Outstanding Lead Actress in a Drama Series. In 2005, Helgenberger won Favorite Female TV Performer at the 31st People's Choice Awards.

Helgenberger announced her departure in 2011, with Catherine making her last appearance in the twelfth season episode "Willows in the Wind", which aired on January 25, 2012. In August 2013, it was announced that Helgenberger would make a guest appearance in the show's 300th episode "Frame By Frame". Catherine appeared in a series of newly recorded flashbacks to a case that occurred in the timeframe of the first season.

The character of Catherine is based on real-life forensics officer Yolanda McClary of the Las Vegas Metropolitan Police. Helgenberger met with McClary and talked about her job in forensics in preparation for the role. The Actress stated that McClary helped her to understand why she enjoyed working the job. Starting in 2013, McClary appeared prominently on Cold Justice, a reality series devoted to reexamination of unsolved cold case murders usually alongside small-town police who have limited investigative resources.

During a particularly difficult case involving her old school friend, Catherine is offered a job with the FBI. She accepts, and, before leaving Las Vegas, instills some sage advice upon Morgan Brody, paralleling her first conversation with Holly Gribbs in the pilot episode. Catherine returns to CSI in 2015, after three years working at the Los Angeles FBI Field Office. She is granted the position of Director of the Las Vegas Crime Lab.